It is now well established that two of the most important biological methods for detoxifying arsenate/arsenite are by binding to tissue proteins and by methylation using enzymes such as methyl-transferases. We have begun the isolation and characterization of specific arsenite-binding proteins and the enzymes that biotransform and detoxify arsenate/arsenite. Super dumps usually are contaminated with mixtures of toxic wastes. Once the proteins involved in decreasing arsenic toxicity have been characterized, other metals such as lead, selenium, cadmium, as well as halogenated aromatic hydrocarbons, will be studied to see if they inhibit these arsenite-binding proteins and methyltransferase biotransformation enzymic reactions for arsenic. The control and regulation of the purified enzymes will be studied and inhibitors and stimulators of the enzymes will be identified. Rabbit and human livers will be the main starting materials for arsenite-binding proteins, enzyme purification. The choroid plexus, where the CSF is manufactured, will be used as one of the sources of arsenite-binding protein(s). The characterization of these proteins and enzymes may yield helpful information to explain the apparent species specificity of arsenic carcinogenicity and the different sensitivities of populations to arsenic. In addition, the role of intracellular glutathione to reduce As+5 to As+3 in the red blood cell and its role in modifying As+3 toxicity will be investigated.